Spontaneous Organization of Phenotypes during Collective Migration

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Project Summary Bacteria live in structured communities where coordinated interactions between individuals often result in collective behaviors beneficial to the population. At the same time, even isogenic bacteria display phenotypic heterogeneity, which diversifies individual behavior and enhances the resilience of the population in unexpected situations. Understanding how the interplay of diversity and collective behavior contributes to spatial organization and function in cell populations is a fundamental problem in cell biology that has been difficult to tackle experimentally and theoretically because of difficulties in measuring and modeling processes at multiple scales. Here we focus on how phenotypic diversity in motility and chemotactic ability contributes to the spatial organization and phenotypic composition of a population of bacteria as it migrates through diverse environments. Our starting point is the recent discovery by us and others that when chasing traveling fronts of attractant generated by their own consumptions, bacteria spontaneously sort themselves along the traveling gradient: high- performing phenotypes localize at the front where the signal (gradient steepness) is weaker and low-performing phenotypes at the back where the signal is stronger but the risk of falling behind is higher. Thus, a leader-follower organization of the phenotypes emerges, even in isogenic populations, with leaders driving the migration and followers falling off and colonizing space behind the moving front. These observations raise the following basic questions: 1) How do phenotypes reorganize themselves when the population encounters a different environment where the most performant phenotype is now different? What does that tell us about the capacity of a single genotype to navigate as a group through multiple environment? 2) To what extent can cell growth partially compensate for the leakage of cells and how does this affect the phenotypic composition and organization of the migrating population? 3) To what extent does the spatial sorting of motility and chemotaxis phenotypes seed spatial organization of virulence factors that tend to be coregulated? To address these questions, we will develop new mathematical models of collective bacterial migration that include three key ingredients: a continuum of phenotypes, cell growth, and diverse environments. To constrain models, we will use E. coli chemotaxis because it is well-characterized, positioning us to discover general principles, and P. aeruginosa, an opportunistic pathogen that shares some features of the E. coli chemotaxis pathway but expresses two different stator systems necessary for migration through different environments.